Cell surface polysaccharides of Bifidobacterium bifidum induce the generation of Foxp3 + regulatory T cells

Sci Immunol. 2018 Oct 19;3(28):eaat6975. doi: 10.1126/sciimmunol.aat6975.

Abstract

Dysregulation of intestinal microflora is linked to inflammatory disorders associated with compromised immunosuppressive functions of Foxp3+ T regulatory (Treg) cells. Although mucosa-associated commensal microbiota has been implicated in Treg generation, molecular identities of the "effector" components controlling this process remain largely unknown. Here, we have defined Bifidobacterium bifidum as a potent inducer of Foxp3+ Treg cells with diverse T cell receptor specificity to dietary antigens, commensal bacteria, and B. bifidum itself. Cell surface β-glucan/galactan (CSGG) polysaccharides of B. bifidum were identified as key components responsible for Treg induction. CSGG efficiently recapitulated the activity of whole bacteria and acted via regulatory dendritic cells through a partially Toll-like receptor 2-mediated mechanism. Treg cells induced by B. bifidum or purified CSGG display stable and robust suppressive capacity toward experimental colitis. By identifying CSGG as a functional component of Treg-inducing bacteria, our studies highlight the immunomodulatory potential of CSGG and CSGG-producing microbes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bifidobacterium bifidum / cytology
  • Bifidobacterium bifidum / immunology*
  • Forkhead Transcription Factors / immunology*
  • Inflammation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Polysaccharides / immunology*
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Polysaccharides